Perception of extracellular signals by cell surface receptors is of central importance to eukaryotic development and immunity. Many of these receptors possess intrinsic protein kinase activity in their cytoplasmic domains (RKs) and regulate transcription of target genes through phosphorylation events. Abnormal regulation can lead to a variety of diseases and it is therefore important to understand how RK specificity and function are controlled. The rice Xa21 RK is a key recognition and signaling determinant in the innate immune response, a pathogen defense pathway widely conserved between plants and animals. XA21 serves as a pathogen recognition receptor (PRR) with leucine rich repeats (LRRs) in the extracellular domain and a non-RD kinase domain. Xa21 activity is triggered upon recognition of the pathogen-associated molecular pattern (PAMP) AvrXa21, a sulfated peptide that is produced by the Gram-negative bacterium Xanthomonas oryzae pv. oryzae. We have shown the XA21 JM domain plays a key role in XA21 kinase-mediated signal transduction. In particular, the XA21 JM amino acid residue serine 697 is critical for both positive and negative regulatory functions. When S697 is dephosphorylated, XA21-mediated resistance is enhanced. Upon phosphorylation, S697 serves as a high affinity-binding site for the downstream negative regulators, XB10 and XB15. We and others have also shown that XA21 is cleaved at the JM domain after treatment with Xoo strains carrying AvrXa21. We hypothesize that, upon AvrXa21-triggered cleavage, the XA21 kinase domain is translocated to the nucleus where it affects downstream signaling through interaction with Xb10 and other proteins. To further test this hypothesis we propose to: 1. Explore AvrXa21-dependent translocation of the XA21 kinase domain to the nucleus. 2. Further characterize the role of XA21S697 JM residue in XA21-mediated resistance. 3. Identify nuclear complexes that form after AvrXa21 activation RKs are an important class of molecules that mediate fundamental processes in both plants and animals. Regulation of RK signaling through the JM domain is so far unique to only a few receptor families controlling important cellular processes and consequently there is great interest in exploring the molecular basis for this control. The proposed studies will enhance our understanding of the role of JM domain cleavage and nuclear translocation of the liberated cytoplasmic domain. Because the XA21 PRR is a model for non-RD mediated innate immunity and receptor-kinase mediated signaling in plants and animals, the experiments proposed here will be broadly applicable to public health.